Oxalyl chloride → Ethyl 6-chloro-7-(4-(2-(2-cyclopropyl-6-(trifluoromethyl)pyridin-3-yl)ethylcarbamoyl)phenoxy)chroman-4-carboxylate

HRID 1626526Notes

Reaction equation

HRID 1626526 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][C:13]1[CH:21]=[CH:20][C:16]([C:17](O)=[O:18])=[CH:15][CH:14]=1)[O:8][CH2:7][CH2:6][CH:5]2[C:22]([O:24][CH2:25][CH3:26])=[O:23].C(Cl)(=O)C(Cl)=O.[CH:33]1([C:36]2[C:41]([CH2:42][CH2:43][NH2:44])=[CH:40][CH:39]=[C:38]([C:45]([F:48])([F:47])[F:46])[N:37]=2)[CH2:35][CH2:34]1.C(N(C(C)C)CC)(C)C>ClCCl.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][C:13]1[CH:21]=[CH:20][C:16]([C:17](=[O:18])[NH:44][CH2:43][CH2:42][C:41]3[C:36]([CH:33]4[CH2:35][CH2:34]4)=[N:37][C:38]([C:45]([F:48])([F:46])[F:47])=[CH:39][CH:40]=3)=[CH:15][CH:14]=1)[O:8][CH2:7][CH2:6][CH:5]2[C:22]([O:24][CH2:25][CH3:26])=[O:23]

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 582443954-(6-Chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acidHCID 672872742-(2-Cyclopropyl-6-(trifluoromethyl)pyridin-3-yl)ethanamine

Product 1

HCID 67288014Ethyl 6-chloro-7-(4-(2-(2-cyclopropyl-6-(trifluoromethyl)pyridin-3-yl)ethylcarbamoyl)phenoxy)chroman-4-carboxylateYield 19.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

4-(6-Chloro-4-(ethoxycarbonyl)chroman-7-yloxy)benzoic acid (Preparation B; 50 mg, 0.13 mmol) was diluted with dichloromethane (2 mL) followed by the addition of oxalyl chloride in dichloromethane (2M) (73 μL, 0.15 mmol) and DMF (1 drop). After stirring for 15 minutes, 2-(2-cyclopropyl-6-(trifluoromethyl)pyridin-3-yl)ethanamine (31 mg, 0.13 mmol) and diisopropyl ethylamine (69 μL, 0.40 mmol) were added. After stirring for 1 hour, the reaction was loaded onto silica gel and eluted with 100% ethyl acetate to yield ethyl 6-chloro-7-(4-(2-(2-cyclopropyl-6-(trifluoromethyl)pyridin-3-yl)ethylcarbamoyl)phenoxy)chroman-4-carboxylate (15 mg, 0.025 mmol, 19% yield). MS (es+apci, positive) m/z=589.2.

Workup

  1. stirringAfter stirring for 1 hour
  2. washeluted with 100% ethyl acetate

Sources & evidence

ORD record
ord-1dce65c60f1f4d29a7b00af82441fe4a
Source dataset
uspto-grants-2014_07
Patent number
US08785445B2

Reaction notes

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